Familial adult myoclonus epilepsy : a clinical, neurophysiological and genetic study of a familial form of myoclonic epilepsy

ENGLISH ABSTRACT: Progressive Myoclonic Epilepsies (PME) are characterized by progressive neurological
impairment with myoclonus, seizures and dementia. In contradistinction, Familial Adult
Myoclonic Epilepsy (FAME) is characterized by a benign course with rare seizures and
cortical tremor. Both conditions have neurophysiological features suggestive of a cortical
origin for their myoclonus.
This dissertation reports on a novel form of PME. Many of those who were affected had no
or minimal progression of their illness, low seizure frequency and were cognitively intact,
suggestive of non-progressive disorders linked to the FAME loci.
The majority of patients had features of cortical myoclonus, with generalized spike and wave
discharges on electroencephalography, enlarged evoked potentials, enhanced C reflexes,
and evidence of cortical excitability with magnetic stimulation. However, there was evidence
of cerebellar dysfunction both pathologically and on imaging. With regard to similar
conditions, dentatorubral pallidoluysian atrophy and Unverricht-Lundborg syndrome were
excluded by linkage analysis. Similarly, linkage was not present for either the FAME 1 or
FAME 2 loci.
This syndrome is both clinically and genetically novel, and has a nosology which is difficult to
characterize, in which the condition appears to lie on the spectrum between FAME and
PME. The dissociation between the pathological and radiological findings which suggest
subcortical dysfunction, and the neurophysiological findings of cortical myoclonus is striking.
Review of the literature associated with the neurophysiology of related conditions associated
with PME and FAME suggests that:
1. The assumption that generalized forms of myoclonic disorders represent multifocal
forms of focal cortical discharges is an oversimplification.
2. The dissociation between initial and later components of the evoked potential is less
robust than is generally supposed, and that subcortical inputs may affect later
components of the evoked potential.
3. In a high proportion of cases the latency from cortical spike discharge to myoclonic
jerk obtained with jerk locked averaging is incompatible with a cortical origin for the
spike discharge.
4. The proposal that myoclonus is a form of long latency reflex and that myoclonus
represents a reflex arising from subclinical sensory input, is unproven.